Method for treating bronchial diseases

ABSTRACT

Administration of a loop diuretic in nebulized dry powder form directly to a patient&#39;s lungs for treating bronchial disease.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims benefit from U.S. Provisional Patent ApplicationSer. No. 60/359,218, filed Feb. 22, 2002.

FIELD OF THE INVENTION

The present invention relates to treatment of patients to providebronchial relief.

BACKGROUND OF THE INVENTION

Bronchial diseases such as asthma, emphysema, cystic fibrosis, dyspnea,chronic bronchitis, and chronic obstructive pulmonary disease (COPD), isa major health problem affecting millions of people worldwide. Themagnitude of bronchial diseases has placed emphasis on the need todevelop new treatment strategies.

Currently, the conventional treatment of asthma and other bronchitisdiseases involves the use of steroids such as prednisone, which isadministered orally, and other steroids and beta adrenergics such asalbuterol, which are administered via an inhaler. However, suchtreatments have significant adverse side affects.

It is therefore an object of the invention to provide an alternativetreatment for bronchial diseases that does not suffer from the usualadverse side affects of conventional treatments.

BRIEF DESCRIPTION OF THE INVENTION

I have found that loop diuretics such as Furosemide(4-chloro-N-(2-furylmethyl)-5-sulfamoyl anthranilic acid) or ethacrynicacid when administered in nebulized dry powder form directly to apatient's lungs advantageously may be used for treating bronchialdisease.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENT

Furosemide is a well-known diuretic agent of the formula I

and its effects have been studied extensively. The drug usually is givenorally, i.e., in table form, but can be administered in solutionintravenously to promote diuresis.

U.S. Pat. No. 4,908,382 to Bianco describes the administration byinhalation in a solution in water of Furosemide, i.e., by means of anebulizer, advantageously may be employed in preventing exercise-inducedbroncho-constriction.

In the present invention, nebulized dry powder loop diuretic such asFurosemide or ethacrynic acid is used to relieve bronchial constriction.Delivery of a loop diuretic in dry powder form is advantageous in thatit permits delivery of the drug conveniently and optimally into thelungs.

Loop diuretics such as ethacrynic acid and Furosemide are availablecommercially from a variety of manufacturers in both tablet and solutionform. Alternatively, Furosemide may be produced following the teachingsof U.S. Pat. No. 5,739,361 to Signor et al., which patent isincorporated herein by reference. For optimal delivery to the lungs, drypowder form of the loop diuretic should be micronized or spray dried toa powder size of 0.5-10 microns, preferably 1-6 microns.

The dry powder loop diuretic may then be put into a conventional drypowder inhaler (DPI) in a systemically effective unit dose deliveryamount between about 1 and 100 milligrams of the loop diuretic, asneeded, typically 1 to 4 times per day.

The dry powder delivery of a loop diuretic to the respiratory tract canbe used advantageously to treat asthma, emphysema, cystic fibrosis,dyspnea, chronic bronchitis, and chronic obstructive pulmonary disease(COPD). Unexpectedly, administration of dry powder Furosemide directlyto the lungs does not produce diuresis.

The following examples are provided to further illustrate the presentinvention.

Example 1

Furosemide in crystalline form is prepared following Example 3 of theU.S. Pat. No. 5,739,361. The resulting crystalline powder is micronizedto a maximum particle size of about 10 microns. The powder is packagedfor unit dose delivery of 10 milligrams in a dry powder inhaler (DPI)made in accordance with my earlier U.S. Pat. No. 6,026,809.

Example 2

Furosemide was prepared as in Example 1, and packaged for delivery in aDPI as before for delivery of 5 milligrams per dose.

Delivery of 5-40 milligrams of Furosemide delivered as needed was foundto provide relief to patients suffering from asthma, emphysema, cysticfibrosis, chronic bronchitis, COPD and dyspnea.

While the invention has been described in detail herein in accordancewith certain preferred embodiments thereof, many modifications andchanges therein may be affected by those skilled in the art.Accordingly, it is intended that the pended claims cover all suchmodifications and changes as may fall within the spirit and scope of theinvention.

1-9. (canceled)
 10. The method of treatment according to claim 15,wherein the patient suffers from emphysema.
 11. The method of treatmentaccording to claim 15, wherein the patient suffers from cystic fibrosis.12-13. (canceled)
 14. The method of treatment according to claim 15,wherein the patient suffers from dyspnea.
 15. A method for relieving asymptom of pulmonary disease in a patient suffering therefrom, whereinthe pulmonary disease is selected from the group consisting ofemphysema, cystic fibrosis, and dyspnea, comprising delivering directlyto the patient's lungs a systemically effective amount of a non-saltformulation of furosemide and ethacrynic acid in dry powder form,wherein said systematically effective amount of a non-salt formulationis delivered as a fine powder having a particle size of 0.5-10 microns.16. The method accordingly to claim 15, wherein said systematicallyeffective amount of a non-salt formulation is delivered in unit doseamounts of between about 1 and 100 milligrams.
 17. The method accordingto claim 16, wherein said systematically effective amount of a non-saltformulation is delivered in unit dose amounts of between about 5 and 10milligrams.
 18. The method according to claim 15, wherein saidsystematically effective amount of a non-salt formulation is deliveredin discrete doses as needed.
 19. The method according to claim 18,wherein said systematically effective amount of a non-salt formulationis delivered in discrete doses 1-4 times per day.
 20. The methodaccording to claim 15, wherein said systematically effective amount of anon-salt formulation is delivered in dry powder form having a powdersize of 1-6 microns.